Study to Assess Effect of Oral Venetoclax Tablet in Combination With Oral Ibrutinib Capsule on Best Overall Response of Complete Response in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma

Phase 2 Study of the Efficacy and Safety of Venetoclax in Combination With Ibrutinib in Japanese Subjects With Relapsed/Refractory Mantle Cell Lymphoma

Mantle Cell Lymphoma (MCL) is a form of Non-Hodgkin Lymphoma (NHL - cancer of the lymphatic system in blood) where cells from outer edge of the lymph nodes, called mantle zone become cancerous. In Japan, MCL accounts for about 3% of all NHL cases. Some symptoms of MCL are enlarged lymph nodes, stomach pain, fever, night sweats, and weight loss. MCL is not curable with standard therapies and has poor outcomes. The purpose of this study is to evaluate the safety, efficacy and effect of venetoclax in combination with ibrutinib on best overall response of complete response in participants with relapsed (return of disease) or refractory (not responding to treatment) (R/R) MCL.

Venetoclax is an investigational drug being developed for the treatment of MCL. Ibrutinib is a drug approved for the treatment of MCL. Participants will receive venetoclax (increasing doses) and ibrutinib (fixed dose) for approximately 104 weeks, followed by ibrutinib alone. Adult participants with R/R MCL will be enrolled. Around 12 participants will be enrolled in Japan.

Participants will receive oral venetoclax tablet and oral ibrutinib capsule for 104 weeks. After 104 weeks, participants will receive ibrutinib once daily until their disease progresses, or they cannot tolerate the medication, or until they do not want to participate in the study.

There may be a higher treatment burden for participants in this study compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, bone marrow biopsies, checking for side effects, and completing questionnaires.

Study Overview

• Status: Active, not recruiting
• Conditions: Mantle Cell Lymphoma (MCL)
• Intervention / Treatment: Drug: Venetoclax; Drug: Ibrutinib

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 460-0001
      • NHO Nagoya Medical Center /ID# 221958
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital /ID# 221565
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 223299
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital /ID# 221662
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital /ID# 221744
  • Ibaraki
    • Higashi Ibaraki-gun, Ibaraki, Japan, 311-3193
      • National Hospital Organization Mito Medical Center /ID# 224912
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-8530
      • Ishikawa Prefectural Central Hospital /ID# 224896
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 9808574
      • Tohoku University Hospital /ID# 221975
  • Okayama
    • Okayama-shi, Okayama, Japan, 700-8558
      • Okayama University Hospital /ID# 221623
  • Saitama
    • Kawagoe-shi, Saitama, Japan, 350-8550
      • Saitama Medical Center /ID# 224910
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 221812
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 990-9585
      • Yamagata University Hospital /ID# 221573

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically confirmed Mantle Cell Lymphoma (MCL) (tumor tissue) by local testing.
• At least 1 measurable site of disease on cross-sectional imaging that is >= 2.0 centimeters (cm) in the longest diameter and measurable in 2 perpendicular dimensions per Computed Tomography (CT).
• At least 1, but no more than 5, prior treatment regimens for MCL including at least 1 prior rituximab/anti-CD20 containing regimen.
• Failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen.

Exclusion Criteria:

• Prior therapy with ibrutinib or other Bruton Tyrosine Kinase (BTK) inhibitors.

• History of other malignancies, except:

  • Malignancy treated with curative intent and with no known active disease present for >= 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease.
• History or current evidence of central nervous system lymphoma.

• Treatment with any of the following within 7 days prior to the first dose of study drug:

  • Moderate or strong cytochrome P450 3A (CYP3A) inhibitors.
  • Moderate or strong CYP3A inducers.
  • Anticancer therapy, including chemotherapy, radiotherapy, small molecule, and investigational agents, and/or monoclonal antibody <=21 days prior to the first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibrutinib + Venetoclax; Participants will receive Ibrutinib Dose A + Venetoclax in various doses until a target dose is reached, for up to 104 weeks, followed by Ibrutinib monotherapy.	Drug: Venetoclax; Tablet; Oral; Other Names: Venclexta; ABT-199; GDC-0199; Venclyxto; Drug: Ibrutinib; Capsule; Oral; Other Names: Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Best Overall Response of Complete Response (CR), as assessed by the Independent Review Committee (IRC)	Best overall response of CR is evaluated using the complete response rate (CRR), defined as the percentage of participants achieving a best overall response of CR for the venetoclax and ibrutinib combination, per the Revised Criteria for Response Assessment as assessed by the Independent Review Committee (IRC).	At Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR), as assessed by the IRC	Best Overall Response of CR or PR will be evaluated using Overall Response Rate (ORR). The ORR is defined as the percentage of participants with a best overall response of CR or PR, according to the Revised Criteria for Response Assessment, as assessed by the IRC.	Up to Approximately 2 Years
Percentage of Participants Achieving Best Overall Response of Complete Response as assessed by the Investigator	Best overall response of CR is defined as the percentage of participants achieving a best overall response of CR for the venetoclax and ibrutinib combination, as assessed by the investigator per the Revised Criteria for Response Assessment.	Up to Approximately 2 Years
Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR), as assessed by the Investigator	Best Overall Response of CR or PR will be evaluated using Overall Response Rate (ORR). The ORR is defined as the percentage of participants with a best overall response of CR or PR, according to the Revised Criteria for Response Assessment, as assessed by the investigator.	Up to Approximately 2 Years
Percentage of Participants Achieving Duration of Response (DOR) for a Best Overall Response, as assessed by the Investigator	DOR is defined as the time from the first occurrence of response (CR or PR) to disease progression or death, whichever occurs first, according to the Revised Criteria for Response Assessment, as assessed by the investigator.	Up to Approximately 2 Years
Percentage of Participants Achieving Duration of Response (DOR) for a Best Overall Response, as assessed by the IRC	DOR is defined as the time from the first occurrence of response (CR or PR) to disease progression or death, whichever occurs first, according to the Revised Criteria for Response Assessment, as assessed by the Independent Review Committee (IRC).	Up to Approximately 2 Years
Percentage of Participants Achieving an Undetectable Minimal Residual Disease (MRD) who Achieve a Best Overall Response, as assessed by the Investigator	MRD rate is defined as the percentage of participants with undetectable MRD who achieve a best overall response of CR, according to the Revised Criteria for Response Assessment, as assessed by the investigator.	Up to Approximately 2 Years
Percentage of Participants Achieving Undetectable Minimal Residual Disease (MRD) in Participants who Achieve a Best Overall Response of CR, as assessed by the IRC	MRD rate is defined as the percentage of participants with undetectable MRD who achieve a best overall response of CR, according to the Revised Criteria for Response Assessment, as assessed by the IRC.	Up to Approximately 2 Years
Progression-Free Survival (PFS)	PFS is defined as the time from the date of the first dose of study drug (venetoclax or ibrutinib) to the date of investigator-assessed disease progression, using the Revised Response Criteria for Response Assessment of Malignant Lymphoma, or death from any cause, whichever occurs first.	Up to Approximately 2 Years
Overall Survival (OS)	OS is defined as the time from the date of the first dose of the study drug (venetoclax or ibrutinib) to death from any cause.	Up to Approximately 2 Years

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): February 9, 2022
• Study Completion (Estimated): October 4, 2025

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ibrutinib; Venetoclax; MCL; ABT-199; Imbruvica
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Venetoclax; Ibrutinib
• Other Study ID Numbers: M20-075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes